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Characterization and Validation of Carcinogen-Induced Transformation of Human Cells In Vitro.

Milo-GE; Kurian-P; Nesnow-S
NIOSH 1988:353-378
A study of the anchorage independence (AI) growth of human fibroblasts when treated with a variety of carcinogens was investigated and an attempt was made to investigate its correlation with cellular tumorigenicity using human neonatal foreskin (HNF) fibroblast cell populations. Cytotoxicity was measured by determining the effect on the relative cloning efficiency of exposure to the following chemicals: aflatoxin-B1 (1162658), aflatoxin-B2 (7220817), 1-naphthylamine (134327), 2-naphthylamine (91598), bis(chloromethyl)ether (542881), N,N-bis(2-chloroethyl)2- naphthylamine (494031) (chloronaphazine) and cyclophosphamide (50180). Toxicity varied widely with 1-naphthylamine and 2- naphthylamine producing less than 25 percent inhibition of the cloning efficiency at 100 microgram/milliliter (microg/ml) treatment medium, while 50microg/ml of aflatoxin-B1 and aflatoxin-B2 inhibited 95 percent and 30 percent, respectively. The variation in cytotoxicities may be due to the varying ability of the cells to metabolize each compound. The two direct acting carcinogens, bis(chloromethyl)ether and chloronaphazine exhibited almost 100 percent inhibition of the cloning efficiency at 10microg/ml. Tests were conducted with aflatoxin-B1, 1-naphthylamine and 2- naphthylamine both with and without uninduced human S-9 liver mix. A dose dependent increase was noted in the number of colonies at lower concentrations of aflatoxin-B1 and 1-naphthylamine while a decrease at high concentrations was noted with a further increase at the highest concentrations, 50microg/ml. Addition of human uninduced S-9 liver mix to the treatment medium increased the number of AI colonies at all concentrations of 2-naphthylamine and at three of the five concentrations of aflatoxin-B1.
Carcinogenesis; Tumorigenesis; Cell-cultures; Cell-function; Cell-morphology; Antineoplastic-agents; Metabolic-study; Mycotoxins; Amines; In-vitro-studies;
1162-65-8; 7220-81-7; 134-32-7; 91-59-8; 542-88-1; 494-03-1; 50-18-0;
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Proceedings of the Fourth NCI/EPA/NIOSH Collaborative Workshop, Progress on Joint Environmental and Occupational Cancer Studies, April 22-23, 1986, Rockville, Maryland, NIH Publication No. 88-2960